The beneficial effect of plasmapheresis in mixed connective tissue disease with coexisting antiphospholipid syndrome.

The authors report a rare case of a female patient with mixed connective tissue disease (MCTD) with coexisting antiphospholipid syndrome (APS). Five years after the diagnosis of MCTD high concentrations of anticardiolipin (anti-CL) and anti-ß2-glycoprotein (anti-ß2GPI) autoantibodies were present in the patient's serum without thrombotic events. Epstein-Barr virus (EBV) reactivation provoked APS, with the clinical manifestations of livedo reticularis, digital gangrene and leg ulcers. Skin biopsy from the necrotic area showed multiple fibrin microthrombi in the superficial vessels. Corticosteroid pulse therapy, and plasma exchange in combination with synchronized cyclophosphamide was administered, which led to improvement of the digital gangrenes, while no new lesions developed. The number of CD27high plasma cells decreased, and the previous high levels of autoantibodies also normalized in the peripheral blood. In the case of MCTD with coexisting APS combination therapy, including plasmapheresis has beneficial effects.

Establishment of the hu-PBL-SCID mouse model for the investigation of thyroid cancer.

New experimental models of human neoplastic diseases attempt to mimic the human environment that fostered the development of disease in cancer patients. The aim of the present study was to establish a human lymphocyte-engrafted, severe combined immunodeficient (hu-PBL-SCID) mouse model to investigate thyroid cancer and to evaluate the potential use of this model for cancer immunotherapy. Thyroid neoplastic tissues were obtained from ten patients (one follicular adenoma, five papillary, one follicular, one anaplastic and two medullary cancers). One 8 x 4 x 3 millimeter sample from each tumor was cut into two pieces of identical size and transplanted into two SCID mice. In each case, one of the two mice was injected intraperitoneally with lymphocytes from the same tumor patient for the reconstitution of the human immune system (Group A), while the other animal received no lymphocytes (Group B). The engraftment of the tumors was successful in all cases. The growth rate was highly dependent on the histological type. When histologies were compared before implantation and after the removal of the implants, the characters of the tumors proved to be unchanged, except one case where an anaplastic cancer arose from a papillary tumor. Macrophages were present in all but one papillary cancer. All differentiated thyroid cancers were infiltrated by T and B lymphocytes. Lymphocytes and macrophages disappeared from 19/20 grafts by week 16. However, in one case from group A lymphocytes were detected four months after the transplantation. In another case from group A, one papillary cancer spontaneously decreased in size and disappeared. Before implantation, HLA-DR expression was detected in every papillary cancer. HLA-DR expression in the grafts was not seen in 3/5 cases by week 16. In conclusion, an animal model has been established for the investigation of human thyroid cancer, by which the analysis of anti-tumor immunity, as a postulate of immune therapy, may be possible.

Investigation of c-myc oncogene amplification in colorectal cancer.

Tumour DNA samples of 20 patients with colorectal carcinoma were tested for c-myc amplification, using a quantitative dot-blot hybridization. Statistical analysis involving clinical and histological parameters like degree of differentiation, Dukes' stage, TNM staging system, age, sex and severity of disease, was applied to estimate the prognostic value of c-myc amplification. The amplification of the investigated oncogene--1.61-fold on the average--was found to significantly correlate with the presence of distant metastasis (corr. coeff.: 0.506, P < 0.05) and the severe course of the disease (corr. coeff.: 0.468, P < 0.05). This result supports the hypothesis that tumour cells with c-myc amplification represent a more malignant and aggressive phenotype. It is also worth noting that both c-myc amplification and formation of distant metastasis are late events in the progression of colorectal cancer, which accounts for the more severe course of the disease.

Investigation of c-myc and K-ras amplification in renal clear cell adenocarcinoma.

Tumour DNA samples isolated from 36 patients with renal clear cell carcinoma were investigated for c-myc and K-ras amplification, using a quantitative dot-blot hybridization. The characteristic clinical and histological parameters involved in the statistical analysis were age, sex, histological grade of the tumour, the TNM staging system, tumour size and weight, vascular invasion and the quality of life. The goal of the study was to estimate the prevalence as well as the prognostic value of the amplification of the oncogenes in question. Amplified c-myc (2.47-fold on the average) was found in three specimens (8.3%), showing slight correlation with intravasation (P > 0.05, n.s.). K-ras amplification (2.93-fold) detected in six tumours (16.6%) was shown to significantly correlate with both histological grade (2.2 vs. 1.8, P < 0.05) and tumour size (15 vs. 8 cm, P < 0.05). In cases with amplified K-ras also lymph node involvement was somewhat more frequent (P > 0.05, n.s.). No coamplification of these oncogenes was observed. The results of the study suggest that K-ras amplification may account for a more rapid progression of the disease.

Myelofibrosis in systemic lupus erythematosus.

In this study we present a case of coexisting systemic lupus erythematosus (SLE) and myelofibrosis. Literature review supports the fact that the two diseases rarely occur together in the same patient. The young female patient studied was admitted with pancytopenia and a clinical picture which met the criteria of SLE. Histological examination of the bone marrow biopsy revealed severe myelofibrosis with hypocellularity of the myeloid cell lines. Treatment with immunosuppressive and colony stimulating factor led to slow but complete regeneration of the bone marrow and subsequently to an improved haematological status, and the patient was spared bone marrow transplantation.

FDG PET imaging in hereditary thyroid cancer.

AIM: To report the role of different imaging methods in staging individuals with multiple endocrine neoplasia 2A (MEN2A) or familial medullary thyroid carcinoma (FMTC). MATERIAL AND METHODS: Fourteen newly diagnosed gene carriers underwent cervical ultrasound scanning (US), cervical and mediastinal CT, MRI and whole-body meta-[131I]iodobenzylguanidine (MIBG) scintigraphy and [18F]fluorodeoxyglucose (FDG) PET scanning. RESULTS: US identified seven true primary cancer. CT and MRI located only tumors > or =5 mm in diameter. MIBG scintigraphy and FDG PET could not identify MTC foci within the thyroid. Whole-body FDG PET identified two true-positive and one false-positive lymph node metastases. MIBG scintigraphy did not identify lymph node metastases. Total thyroidectomy was performed in 12 cases, and subtotal thyroidectomy in two subjects. CONCLUSIONS: Whole-body FDG PET and cervical US help stage individuals carrying mutant genes verifying MEN2A or FMTC.

C-myc amplification and cluster analysis in human gastric carcinoma.

The tumour samples ot 23 patients (9 male, 14 female, aged 28-85) were randomly selected for the study. DNA was isolated from paraffin embedded tissue for quantitative dot-blot hybridization, in order to determine the amplification values for the c-myc and K-ras oncogenes. The clinical and histological parameters studied were as follows: grade, TNM staging system, Lauren's histological type, localization and the severity of the disease. Amplified c-myc was found in 6 cases. Amplification was concomitant with c-myc overexpression detected with immunohistochemical staining. The amplification--9.1-fold on the average (ranging from 2.12 to 18.2) was significantly associated with the presence of distant metastasis (corr. coeff.: 0.5623, p < 0.01), but with none of the other parameters. No case with K-ras amplification was recorded. The result of the multivariate cluster analysis proved that age was the decisive factor in the segregation process. This age-related distribution (69 vs. 40, p < 0.001), however, did not coincide with either the incidence of distant metastasis or c-myc amplification.

Cerebral effects of a single dose of intravenous vinpocetine in chronic stroke patients: a PET study.

The effects of vinpocetine (Cavinton) on the cerebral glucose metabolism of chronic stroke patients are studied with positron emission tomography. The regional and global cerebral metabolic rates of glucose (CMRglu) and the kinetic constants related to them are quantified before and after single-dose intravenous vinpocetine treatment. These measurements are completed with transcranial Doppler sonography and single photon emission computed tomography to explore the possible mechanisms underlying the resulting changes in glucose uptake and metabolism in the brain. The authors' findings indicate that a single-dose vinpocetine treatment, although it does not affect significantly the regional or global metabolic rates of glucose, improves significantly the transport of glucose (both uptake and release) through the blood-brain barrier in the whole brain, the entire contralateral hemisphere, and in the brain tissue around the infarct area of the symptomatic hemisphere. These changes are in accord with increased blood flow in the entire contralateral hemisphere as well as decreased blood flow velocity and increased peripheral vessel resistance in the entire symptomatic hemisphere.

The angiographic appearance of renal angiomyolipoma and problems of its preoperative diagnosis.

The radiodiagnostic difficulties of renal hamartoma (renal angiomyolipoma) have been discussed in connection with the authors' two cases. In the first case a unifocal cystic renal angiomyolipoma without tuberous sclerosis caused retroperitoneal haematoma and acute symptoms. In the second case a preoperative tentative diagnosis of angiomyolipoma was made, however, the Pringle-type dermal lesions were only observed 6 months after surgery on control examination. The authors state that the radiographic functional findings vary depending on the tissue structure of the tumour. Differential diagnosis of cystic angiomyolipoma containing little fatty and angiomatous tissue is impossible, whereas for the hypervascular variant a tentative diagnosis can be established even in the case of unifocal hamartoma.

[Cerebral deep vein thrombosis associated with rectal cancer]. / Rectumcarcinomával társult agyi mélyvénás thrombosis.

The authors report a case where the patient suffered from deep cerebral venous thrombosis, which developed beside cerebral metastases of a colorectal cancer. The pathogenesis and diagnosis of this disease are also discussed. This rare location of thrombosis is mainly due to hypercoagulable state seen in the use of oral contraceptive drugs, Behçet syndrome, nephrotic syndrome, and as paraneoplastic syndrome in malignant diseases. Literature reports less than 50 cases of deep cerebral venous thrombosis, of which less than 10 are evoked by malignant disease. The symptoms of DCVT can mimic cerebral metastases in cancer patients. The course of disease is aggressive, the prognosis is poor. Even if the patients survive considerable neurological deficits may remain. Authors emphasize the importance of current modern diagnostic imaging methods in the diagnosis. The possibility of deep cerebral venous thrombosis must be taken into account if sudden neurological symptoms develop in a cancer patient.

[Association of carcinoid tumor of the appendix and Crohn disease (case report and review of the literature)]. / Appendix carcinoid tumor és Crohn-betegség társulása (esetismertetés és irodalmi áttekintés).

The authors describe the coexistence of the carcinoid of the appendix and Crohn's disease. In the case of their woman patient the carcinoid was identified with the examination of the resected ileoascendent part of the bowel resulting of the complication of the Crohn's disease. 10 similar association is known in the literature but none of the patients had the signs of the carcinoid syndrome. Subsequent adrenerg syndrome after an alimentary hypoglycemia (increased evacuation of the cathecolamines and their metabolites in the urine), food allergy (increased IgE type antibody to milk protein) or gastroenteropancreatic (GEP) neuroendocrine tumor (based on the result of the 111In-octreoscan and the increased 5-hydroxyindolaceticaciduria) equally suspected of the symptoms (palpitation, flush) manifested after the operation. They look for the connection between the genesis of the intestinal carcinoid and the Crohn's disease with working up the bibliography. Summing up the references with a view of the latest it can be stated that the carcinoid of the appendix occurs more than orders of magnitude in the samples from inflamed surrounding than the samples from autopsy (0.24%--820/338,000 inflamed appendix and 0.03%--19/53,430 appendix from autopsy). Consequently the inflammation create favourable condition for the development of the carcinoid of the appendix.

[Detection of Helicobacter pylori in tissue samples of stomach cancer]. / A Helicobacter pylori kimutatása gyomorcarcinomás szöveti mintákban.

The role of Helicobacter pylori in the carcinogenesis of the stomach has been recognised both in intestinal and diffuse forms. The occurrence of the bacterium was studied in this report, with various methods in biopsy samples from the cancerous stomach, as well as the presence of associated gastritis and metaplasia related to the histological type. Retrospective histological examination were performed on endoscopic biopsy samples from 124 patients with distal stomach cancer using haematoxillin-eosin and Giemsa staining and immunohistochemical tests. Out of the 124 samples 69 (55.64%) was positive: 48 with Giemsa staining and further 21 samples showed immunohistochemical positivity on atrophic gastritis samples despite negative Giemsa staining. In view of the presence of gastritis and metaplasia significant difference (p < 0.001) was found between the positive and negative cases. The ratio of the Helicobacter pylori positive samples was high both for intestinal and diffuse type carcinomas. Our results suggest that the presence of Helicobacter pylori infection is important in the development of both types of carcinoma, nevertheless, the hystological type of the tumor is also decisively influenced by the onset of action of other more direct local eliciting factors.

[Prediction of the result of high-risk coronary bypass surgery by positron emission tomography]. / Nagy kockázatú koszorúér bypass mütét eredményességének elörejelzése pozitron emissziós tomográfiával.

Coronary angiography revealed three-vessel disease in a 56-year-old male with two previous myocardial infarctions. Coronary bypass surgery was initially ruled out by cardiac surgeon because of the poor left ventricular function (EF: 23%), despite moderate viability signs during conventional isotope techniques. Positron emission tomography with 18FDG indicated a large periinfarction area of hibernating myocardium. Accordingly, coronary bypass grafting was performed. Postoperatively, the symptoms disappeared, the left ventricular wall motion abnormalities (with the exception of the scarred region demonstrated by PET) improved, and the global left ventricular function increased significantly. This case and the role of cardiac PET study for prediction of the result of revascularization are discussed.

[Bilateral primary lymphoma of the breasts detected in pregnancy]. / Terhesség során felismert kétoldali, primer emlólymphoma.

The authors report a case of bilateral primary malignant lymphoma of the breast presenting during pregnancy in a 24-year-old woman. After delivery of a healthy premature infant by Caesarean section, polychemotherapy was employed. The efficacy of the treatment could not be evaluated since the patient died within a very short period of time. Autopsy and histological examination revealed infiltration of Burkitt-type lymphoma in the breast, ovary, brain, liver, kidney, adrenal gland, pancreas, stomach, bone marrow and myocardium.

[Diagnosis of Meckel diverticulum, containing ectopic gastric mucosa", by studying small bowel passage]. / Ectopiás gyomornyálkahártyát tartalmazó Meckel-diverticulum felismerése vékonybél-passage vizsgálattal.

Radiological diagnosis of Meckel diverticulum is a difficult task. Here we report a patient with hereditary sphaerocytosis who complained of a chronic periumbilical pain and in whom antegrade barium enema suggested Meckel diverticulum. The diagnosis had been proven both surgically and histologically. This observation indicates that so called traditional x-ray still has its role even in the era of modern (and expensive) radiology.

[Catastrophic antiphospholipid antibody syndrome in a cancer patient]. / Antifoszfolipid katasztrófa-szindróma daganatos betegben.

Antiphospholipid syndrome is characterized by the presence of antiphospholipid antibodies resulting in arterial and venous thromboembolism. Apart from primary cases, this syndrome is often associated with autoimmune diseases. Around 50 cases of catastrophic antiphospholipid antibody syndrome have been reported as yet. Authors describe a case of a female patients with catastrophic antiphospholipid syndrome associated with gastric cancer. This may be the first case of such association in the literature. Authors also discuss the possible pathomechanism of this disorder, as well as the available therapeutic approaches.

[Cerebral positron emission tomographic study in systemic lupus erythematosus]. / Agyi pozitron emissziós tomográfiai vizsgálatok systemás lupus erythematosusban.

The cerebral glucose metabolism in eight patients with systemic lupus erythematosus (SLE) and in five healthy controls were examined by positron emission tomography (PET) using 18-F-labeled deoxy-glucose (FDG) as tracer. One of the eight patients had no abnormality by magnetic resonance imaging (MRI), three of them had cerebral atrophy and four patients had multiple white matter hyperintensities and vascular infarcts in the striatum as assessed by MRI. With FDG-PET, inhomogeneous multifocal cerebral glucose hypometabolism was detected, more frequently in the temporal lobe of right hemisphere. The PET findings did not correlate always with the neurological symptoms. Abnormalities in brain metabolism can be detected more frequently by PET, than morphological changes by MRI, indicating the involvement of the central nervous system.

[11C-methionine: an effective radio-tracer for PET scan in the detection of tumors of low proliferating capacity]. / 11C-metionin: hatékony radiofarmakon az alacsony proliferatív kapacitású daganatok PET-vizsgálatához.

11C-methyl-methionine is available at the PET Center of University Medical School Debrecen since June, 1996. The first 5 oncological examinations were indicated for clinically suspected recurrent/residual tumorous tissue of low-grade/low proliferative capacity, following the negative or inconclusive results of previous 18F-deoxyglucose (FDG) examinations. In these situations, the methionine examinations provided conclusive results in 4 cases (out of the total of 5 examinations). On the basis of published data and own experience, the authors recommend methionine PET investigations for diagnosis, differential diagnosis and therapy monitoring of tumours of low-grade/low proliferative capacity following inconclusive results of previous FDG examination.

[Evaluation of the nature of brain tumors using methods of nuclear medicine]. / Agydaganatok természetének vizsgálata nukleáris medicinai módszerekkel.

FDG-PET studies permit an assessment of the degree of brain tumour malignancy and detection of tumour recurrence. MIBI-SPECT also affords promising results in this respect. In this work, the diagnostic value of MIBI-SPECT was compared with that of FDG-PET for the determination of primary brain tumours malignancy and the detection of recurrent brain tumours. SPECT and PET examination were carried out within a week in 14 patients (12 males, 2 females, mean age: 40 years, range 16-61 years) with brain tumours. Seven patients had a primary tumour, and in a further 7 MRI or the clinical signs and symptoms let to a suspicion of tumour recurrence. All tumours were verified histologically to be gliomas of grades I-IV. The SPECT and PET images were analysed visually and semiquantitatively. In 3 of the investigated 7 primary glioma patients, there was a visibly enhanced MIBI-positive cases, only one had an increased FDG uptake. In 4 of the 7 tumour recurrence cases, either the MIBI or the FDG uptake was visibly increased. All of these were histologically high-grade gliomas. In the remaining low grade tumours (primary of recurrent), neither MIBI nor FDG revealed a pathologically increased uptake. The intensity of radiopharmaceutical uptake at the site of the tumours was visually and semiquantitatively higher for MIBI that for FDG. It is concluded that MIBI-SPECT is a valuable and simple tool for evaluation of the biological characteristics of brain tumours, showing increased uptake of MIBI according to the malignancy and tumour recurrence of brain tumours.

[Positron emission tomography ia an effective tool in modern oncology]. / A pozitronemissziós tomográfia a korszerü onkológiai ellátás hatékony eszköze.

A total of 399 positron emission tomography (PET) examinations were carried out with a GE 4096 Plus PET scanner during the past 5 years on patients referred to the National Institute of Oncology in Budapest. The majority (n = 316) of these investigations were performed with the use of [18F]-fluorodezoxyglucose (FDG) to map the glucose metabolism; [11C]-methionine PET was indicated in 79 cases to detect protein transport and metabolism. The perfusion tracer [15O]-butanol was applied in only 4 cases to answer certain oncology-related, differential diagnostic questions. The oncological examinations were related to primary diagnostics, staging/restaging and therapy monitoring. In the staging/restaging and therapy monitoring of known tumours, conclusive results were achieved in 81-82% of the cases by using either FDG or [11C]-methionine as tracer. The concordant numerical data indicated that the PET investigation provides a definite answer to the question of the presence or absence of viable tumour tissue, with similar effectivity in any of the above indications, no matter whether FDG or [11C]-methionine is used. The search for occult primary tumours was the most frequent indication within the primary diagnostics: 10 (37%) primaries were localized by using FDG PET in the 27 investigated cases. This is a remarkably high value, especially in view of the failure of all the conventional diagnostic procedures carried out prior to the PET investigations. Application of PET may be indicated in all cases when the ultimate question is a non-invasive estimation of viable tumorous tissue.